TWI783991B - Pd‐1/pd‐l1抑制劑 - Google Patents
Pd‐1/pd‐l1抑制劑 Download PDFInfo
- Publication number
- TWI783991B TWI783991B TW107113386A TW107113386A TWI783991B TW I783991 B TWI783991 B TW I783991B TW 107113386 A TW107113386 A TW 107113386A TW 107113386 A TW107113386 A TW 107113386A TW I783991 B TWI783991 B TW I783991B
- Authority
- TW
- Taiwan
- Prior art keywords
- alkyl
- cycloalkyl
- heteroaryl
- aryl
- heterocyclyl
- Prior art date
Links
- 239000012269 PD-1/PD-L1 inhibitor Substances 0.000 title 1
- 229940121653 pd-1/pd-l1 inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 151
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 20
- 201000011510 cancer Diseases 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 1861
- 125000000623 heterocyclic group Chemical group 0.000 claims description 545
- 125000001072 heteroaryl group Chemical group 0.000 claims description 490
- 125000003118 aryl group Chemical group 0.000 claims description 484
- -1 alkyl NR 1 Chemical compound 0.000 claims description 444
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 267
- 125000005843 halogen group Chemical group 0.000 claims description 262
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 260
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 184
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 169
- 125000003342 alkenyl group Chemical group 0.000 claims description 112
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 110
- 229910052757 nitrogen Inorganic materials 0.000 claims description 102
- 125000000304 alkynyl group Chemical group 0.000 claims description 100
- 229910052717 sulfur Inorganic materials 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 73
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 71
- 229910052760 oxygen Inorganic materials 0.000 claims description 69
- 125000001424 substituent group Chemical group 0.000 claims description 60
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 58
- 125000005842 heteroatom Chemical group 0.000 claims description 58
- 239000001301 oxygen Substances 0.000 claims description 53
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 50
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 44
- 125000004432 carbon atom Chemical group C* 0.000 claims description 38
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 37
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 36
- 239000011593 sulfur Substances 0.000 claims description 36
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 35
- 125000001188 haloalkyl group Chemical group 0.000 claims description 31
- 150000001204 N-oxides Chemical class 0.000 claims description 27
- 125000004434 sulfur atom Chemical group 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 17
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims description 16
- 230000003993 interaction Effects 0.000 claims description 15
- 150000001345 alkine derivatives Chemical class 0.000 claims description 13
- 239000002246 antineoplastic agent Substances 0.000 claims description 13
- 125000006413 ring segment Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 229960003301 nivolumab Drugs 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 229960005386 ipilimumab Drugs 0.000 claims description 7
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001924 cycloalkanes Chemical class 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 5
- 229960003852 atezolizumab Drugs 0.000 claims description 5
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
- 229960002621 pembrolizumab Drugs 0.000 claims description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 4
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 4
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 4
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 4
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 3
- 208000018084 Bone neoplasm Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 3
- 206010039491 Sarcoma Diseases 0.000 claims description 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 3
- 201000007455 central nervous system cancer Diseases 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 239000011574 phosphorus Chemical group 0.000 claims description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 206010042971 T-cell lymphoma Diseases 0.000 claims description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 229960004679 doxorubicin Drugs 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 201000003444 follicular lymphoma Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 229960005277 gemcitabine Drugs 0.000 claims description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 2
- 201000002120 neuroendocrine carcinoma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 claims description 2
- 229960004641 rituximab Drugs 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 102000008096 B7-H1 Antigen Human genes 0.000 claims 2
- 229960000402 palivizumab Drugs 0.000 claims 2
- 125000002355 alkine group Chemical group 0.000 claims 1
- 238000002271 resection Methods 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 50
- 238000011282 treatment Methods 0.000 abstract description 16
- 238000000034 method Methods 0.000 abstract description 14
- 125000002877 alkyl aryl group Chemical group 0.000 description 174
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 39
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 35
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 32
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 31
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 28
- 239000002585 base Substances 0.000 description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- 238000006467 substitution reaction Methods 0.000 description 24
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 22
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 22
- 150000001412 amines Chemical class 0.000 description 21
- 229910052786 argon Inorganic materials 0.000 description 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 20
- 125000004429 atom Chemical group 0.000 description 18
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 15
- 125000003107 substituted aryl group Chemical group 0.000 description 15
- 201000010099 disease Diseases 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 125000004076 pyridyl group Chemical group 0.000 description 14
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 125000001544 thienyl group Chemical group 0.000 description 11
- 229910052721 tungsten Inorganic materials 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 10
- 125000001041 indolyl group Chemical group 0.000 description 10
- 125000001624 naphthyl group Chemical group 0.000 description 10
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 125000004404 heteroalkyl group Chemical group 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 125000003636 chemical group Chemical group 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- 125000000547 substituted alkyl group Chemical group 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 125000000335 thiazolyl group Chemical group 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 239000012453 solvate Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 125000004438 haloalkoxy group Chemical group 0.000 description 4
- 125000001475 halogen functional group Chemical group 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 241000700721 Hepatitis B virus Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000003277 amino group Chemical class 0.000 description 3
- 125000000732 arylene group Chemical group 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 235000019000 fluorine Nutrition 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229910052701 rubidium Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 241001061127 Thione Species 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000002009 alkene group Chemical group 0.000 description 2
- 150000001350 alkyl halides Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical class C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000005265 dialkylamine group Chemical group 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229940083542 sodium Drugs 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- 125000006653 (C1-C20) heteroaryl group Chemical group 0.000 description 1
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 description 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 description 1
- 125000006654 (C3-C12) heteroaryl group Chemical group 0.000 description 1
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 description 1
- 125000006655 (C3-C8) heteroaryl group Chemical group 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 125000005926 1,2-dimethylbutyloxy group Chemical group 0.000 description 1
- UDSAJFSYJMHNFI-UHFFFAOYSA-N 2,6-diazaspiro[3.3]heptane Chemical compound C1NCC11CNC1 UDSAJFSYJMHNFI-UHFFFAOYSA-N 0.000 description 1
- WIGUNJUDINBXPD-UHFFFAOYSA-N 2,7-diazaspiro[4.4]nonan-3-one Chemical compound C1NC(=O)CC11CNCC1 WIGUNJUDINBXPD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- QPEJAHMNOVMSOZ-UHFFFAOYSA-N 2-azaspiro[3.3]heptane Chemical compound C1CCC21CNC2 QPEJAHMNOVMSOZ-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- KPUSZZFAYGWAHZ-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octane Chemical compound C1CC2CCC1NC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- URMVFILWXLQJIP-UHFFFAOYSA-N 4,5,6,7-tetrahydro-3h-imidazo[4,5-c]pyridine Chemical compound C1NCCC2=C1NC=N2 URMVFILWXLQJIP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008761 Choriomeningitis lymphocytic Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical class OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 150000008522 N-ethylpiperidines Chemical class 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000012270 PD-1 inhibitor Substances 0.000 description 1
- 239000012668 PD-1-inhibitor Substances 0.000 description 1
- 239000012271 PD-L1 inhibitor Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Chemical class OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000005466 alkylenyl group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000012635 anticancer drug combination Substances 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000011398 antitumor immunotherapy Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001559 benzoic acids Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000004452 carbocyclyl group Chemical group 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000005266 diarylamine group Chemical group 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical class CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 125000000262 haloalkenyl group Chemical group 0.000 description 1
- 125000000232 haloalkynyl group Chemical group 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 125000005241 heteroarylamino group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229940045207 immuno-oncology agent Drugs 0.000 description 1
- 239000002584 immunological anticancer agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000010983 kinetics study Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical compound COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940121655 pd-1 inhibitor Drugs 0.000 description 1
- 229940121656 pd-l1 inhibitor Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 description 1
- CSHWQDPOILHKBI-UHFFFAOYSA-N peryrene Natural products C1=CC(C2=CC=CC=3C2=C2C=CC=3)=C3C2=CC=CC3=C1 CSHWQDPOILHKBI-UHFFFAOYSA-N 0.000 description 1
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M thiocyanate group Chemical group [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000005259 triarylamine group Chemical group 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/69—Two or more oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762488017P | 2017-04-20 | 2017-04-20 | |
US62/488,017 | 2017-04-20 | ||
US201762507678P | 2017-05-17 | 2017-05-17 | |
US62/507,678 | 2017-05-17 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201902877A TW201902877A (zh) | 2019-01-16 |
TWI783991B true TWI783991B (zh) | 2022-11-21 |
Family
ID=62117030
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW107113386A TWI783991B (zh) | 2017-04-20 | 2018-04-19 | Pd‐1/pd‐l1抑制劑 |
TW112144378A TW202432535A (zh) | 2017-04-20 | 2018-04-19 | Pd‐1/pd‐l1抑制劑 |
TW111141601A TWI835379B (zh) | 2017-04-20 | 2018-04-19 | Pd‐1/pd‐l1抑制劑 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW112144378A TW202432535A (zh) | 2017-04-20 | 2018-04-19 | Pd‐1/pd‐l1抑制劑 |
TW111141601A TWI835379B (zh) | 2017-04-20 | 2018-04-19 | Pd‐1/pd‐l1抑制劑 |
Country Status (30)
Country | Link |
---|---|
US (2) | US20180305315A1 (pt) |
EP (2) | EP3612525B1 (pt) |
JP (3) | JP7161491B2 (pt) |
KR (4) | KR20240096808A (pt) |
CN (2) | CN110799509B (pt) |
AU (4) | AU2018256423B2 (pt) |
BR (1) | BR102018007822A2 (pt) |
CA (2) | CA3175847A1 (pt) |
CL (1) | CL2019002895A1 (pt) |
CO (1) | CO2019011543A2 (pt) |
CR (1) | CR20190478A (pt) |
CY (1) | CY1124891T1 (pt) |
DK (1) | DK3612525T3 (pt) |
DO (1) | DOP2019000266A (pt) |
ES (1) | ES2902360T3 (pt) |
HR (1) | HRP20211920T1 (pt) |
HU (1) | HUE057506T2 (pt) |
IL (1) | IL269466A (pt) |
JO (1) | JOP20180040A1 (pt) |
LT (1) | LT3612525T (pt) |
MA (1) | MA50147A (pt) |
MX (1) | MX2019011431A (pt) |
PE (1) | PE20200177A1 (pt) |
PL (1) | PL3612525T3 (pt) |
PT (1) | PT3612525T (pt) |
SG (1) | SG11201908619TA (pt) |
SI (1) | SI3612525T1 (pt) |
TW (3) | TWI783991B (pt) |
UY (1) | UY37690A (pt) |
WO (1) | WO2018195321A1 (pt) |
Families Citing this family (130)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016057931A1 (en) | 2014-10-10 | 2016-04-14 | The Research Foundation For The State University Of New York | Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration |
EP3365340B1 (en) | 2015-10-19 | 2022-08-10 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
HRP20221035T1 (hr) | 2015-11-19 | 2022-11-11 | Incyte Corporation | Heterociklički spojevi kao imunomodulatori |
AU2016379372A1 (en) | 2015-12-22 | 2018-08-02 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
WO2017192961A1 (en) | 2016-05-06 | 2017-11-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
EP3464279B1 (en) | 2016-05-26 | 2021-11-24 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
JP7000357B2 (ja) | 2016-06-20 | 2022-01-19 | インサイト・コーポレイション | 免疫調節剤としての複素環化合物 |
AU2017289038B2 (en) | 2016-06-27 | 2021-07-22 | Chemocentryx, Inc. | Immunomodulator compounds |
MA45669A (fr) | 2016-07-14 | 2019-05-22 | Incyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
MA46045A (fr) | 2016-08-29 | 2021-04-28 | Incyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
MX2019006206A (es) | 2016-11-29 | 2019-08-14 | Censa Pharmaceuticals Inc | Polimorfos de sepiapterina y sales de los mismos. |
DK3558990T3 (da) | 2016-12-22 | 2022-09-12 | Incyte Corp | Tetrahydroimidazo[4,5-c]pyridinderivater som pd-l1 internaliseringsinducere |
WO2018119266A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Benzooxazole derivatives as immunomodulators |
WO2018119236A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Triazolo[1,5-a]pyridine derivatives as immunomodulators |
MA47120A (fr) | 2016-12-22 | 2021-04-28 | Incyte Corp | Dérivés pyridine utilisés en tant qu'immunomodulateurs |
US11130740B2 (en) | 2017-04-25 | 2021-09-28 | Arbutus Biopharma Corporation | Substituted 2,3-dihydro-1H-indene analogs and methods using same |
IL272258B (en) | 2017-07-28 | 2022-08-01 | Chemocentryx Inc | Immunomodulator compounds |
ES2926540T3 (es) | 2017-08-08 | 2022-10-26 | Chemocentryx Inc | Inmunomoduladores macrocíclicos |
CN111386116B (zh) * | 2017-08-18 | 2022-06-14 | 上海轶诺药业有限公司 | 一种具有pd-l1抑制活性的化合物、其制备方法及用途 |
CA3073957A1 (en) | 2017-09-01 | 2019-03-07 | Censa Pharmaceuticals Inc. | Pharmaceutical compositions comprising sepiapterin and uses thereof |
WO2019122941A1 (en) | 2017-12-21 | 2019-06-27 | Debiopharm International Sa | Combination anti cancer therapy with an iap antagonist and an anti pd-1 molecule |
AU2019222644B2 (en) | 2018-02-13 | 2021-04-01 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
EP3755311A4 (en) | 2018-02-22 | 2021-11-10 | ChemoCentryx, Inc. | USEFUL INDANE-AMINES AS AN AGONISTS OF PD-L1 |
US12083118B2 (en) | 2018-03-29 | 2024-09-10 | Arbutus Biopharma Corporation | Substituted 1,1′-biphenyl compounds, analogues thereof, and methods using same |
EP3774791B1 (en) | 2018-03-30 | 2022-12-21 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
KR102591947B1 (ko) * | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
CA3099994A1 (en) | 2018-05-11 | 2019-11-04 | Incyte Corporation | Tetrahydro-imidazo[4,5-c]pyridine derivatives as pd-l1 immunomodulators |
CN111886219B (zh) * | 2018-07-11 | 2023-04-25 | 上海和誉生物医药科技有限公司 | 免疫抑制剂及其制备方法和在药学上的应用 |
BR112020026746A2 (pt) * | 2018-07-13 | 2021-03-30 | Gilead Sciences, Inc. | Composto, composição farmacêutica, métodos para inibir pd-1, pd-l1 e/ou a interação de pd-1/pd-l1 e para tratar câncer, e, kit para tratar ou prevenir câncer ou uma doença ou condição. |
CN110790758A (zh) * | 2018-08-01 | 2020-02-14 | 上海轶诺药业有限公司 | 一类具有免疫调节功能的含n杂环化合物的制备和应用 |
UY38349A (es) | 2018-08-30 | 2020-03-31 | Array Biopharma Inc | Compuestos de pirazolo[3,4-b]piridina como inhibidores de cinasas tam y met |
AU2019339703B2 (en) * | 2018-09-13 | 2024-06-06 | Betta Pharmaceuticals Co., Ltd | Immunomodulators, compositions and methods there of |
KR102635333B1 (ko) * | 2018-10-24 | 2024-02-15 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
CN111138301B (zh) * | 2018-11-02 | 2024-01-05 | 上海再极医药科技有限公司 | 联苯类化合物、其中间体、制备方法、药物组合物及应用 |
US11596692B1 (en) | 2018-11-21 | 2023-03-07 | Incyte Corporation | PD-L1/STING conjugates and methods of use |
WO2020109328A1 (en) | 2018-11-26 | 2020-06-04 | Debiopharm International S.A. | Combination treatment of hiv infections |
US20200216416A1 (en) | 2019-01-03 | 2020-07-09 | Array Biopharma Inc. | Quinoline compounds as inhibitors of tam and met kinases |
CN109776377B (zh) * | 2019-02-01 | 2021-08-24 | 沈阳药科大学 | 吲哚啉类化合物及其制备方法和应用 |
CN112876458B (zh) * | 2019-02-21 | 2022-10-04 | 厦门宝太生物科技股份有限公司 | 细胞程序性死亡-配体-1拮抗剂化合物 |
CA3134171A1 (en) | 2019-03-22 | 2020-10-01 | Guangzhou Maxinovel Pharmaceuticals Co., Ltd. | Small-molecule inhibitor of pd-1/pd-l1, pharmaceutical composition thereof with pd-l1 antibody, and application of same |
KR20210153665A (ko) * | 2019-05-10 | 2021-12-17 | 상하이 하이옌 파마슈티컬 테크놀로지 컴퍼니, 리미티드 | 치환된 페닐프로펜일피리딘 유도체, 이의 제조 방법 및 이의 의약 용도 |
WO2020232256A1 (en) | 2019-05-15 | 2020-11-19 | Chemocentryx, Inc. | Triaryl compounds for treatment of pd-l1 diseases |
CN110128415B (zh) * | 2019-05-31 | 2022-03-25 | 沈阳药科大学 | 用作免疫调节剂的吲哚啉类化合物及其制备方法 |
WO2020244518A1 (zh) * | 2019-06-04 | 2020-12-10 | 中国科学院上海药物研究所 | 一种具有苄氧基芳环结构的化合物,其制备方法和用途 |
US20220233684A1 (en) * | 2019-06-18 | 2022-07-28 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and pd-l1 inhibitors |
CA3140588A1 (en) * | 2019-06-18 | 2020-12-24 | Helen Horton | Combination of hepatitis b virus (hbv) vaccines and small molecule pdl1 or pd1 inhibitor |
JP2022536845A (ja) * | 2019-06-20 | 2022-08-19 | ケモセントリックス,インコーポレイティド | Pd-l1疾患の治療のための化合物 |
CN114206338A (zh) * | 2019-07-10 | 2022-03-18 | 凯莫森特里克斯股份有限公司 | 作为pd-l1抑制剂的二氢化茚类 |
JP2022544189A (ja) | 2019-08-09 | 2022-10-17 | インサイト・コーポレイション | Pd-1/pd-l1阻害剤の塩 |
CN112457308B (zh) * | 2019-09-09 | 2024-01-02 | 上海长森药业有限公司 | 新型三环芳香杂环化合物,及其制备方法、药物组合物和应用 |
CN112457305A (zh) * | 2019-09-09 | 2021-03-09 | 上海长森药业有限公司 | 含三环结构的芳香杂环化合物,及其制备方法和应用 |
CN112457331A (zh) * | 2019-09-09 | 2021-03-09 | 上海长森药业有限公司 | 含氮杂环类化合物,及其制备方法、药物组合物和应用 |
CN112457329B (zh) * | 2019-09-09 | 2023-08-25 | 上海长森药业有限公司 | 芳香杂环衍生物作为免疫调节剂的制备及其应用 |
CA3155852A1 (en) | 2019-09-30 | 2021-04-08 | Incyte Corporation | PYRIDO[3,2-D]PYRIMIDINE COMPOUNDS AS IMMUNOMODULATORS |
US20220402917A1 (en) | 2019-09-30 | 2022-12-22 | Medshine Discovery Inc. | Compound as small molecule inhibitor pd-1/pd-l1 and application thereof |
AU2020357502A1 (en) | 2019-09-30 | 2022-05-19 | Gilead Sciences, Inc. | HBV vaccines and methods treating HBV |
CR20220215A (es) | 2019-10-16 | 2022-09-14 | Chemocentryx Inc | Heteroaril bifenil amidas para el tratamiento de enfermedades relacionadas con el ligando pd-l1 |
CR20220216A (es) | 2019-10-16 | 2023-01-09 | Chemocentryx Inc | Aminas de heteroaril-bifenilo para el tratamiento de enfermedades pd-l1 |
CN118178645A (zh) | 2019-10-18 | 2024-06-14 | 四十七公司 | 用于治疗骨髓增生异常综合征和急性髓系白血病的联合疗法 |
MX2022005123A (es) | 2019-10-31 | 2022-05-30 | Forty Seven Inc | Tratamiento basado en anti-cd47 y anti-cd20 para cancer hematologico. |
CA3160131A1 (en) | 2019-11-11 | 2021-05-20 | Incyte Corporation | Salts and crystalline forms of a pd-1/pd-l1 inhibitor |
CN112979641A (zh) * | 2019-12-17 | 2021-06-18 | 上海轶诺药业有限公司 | 一类具有免疫调节功能的含n杂环化合物的制备和应用 |
DK4081305T3 (da) | 2019-12-24 | 2024-10-14 | Carna Biosciences Inc | Diacylglycerinkinase modulerende forbindelser |
IL294209A (en) * | 2019-12-26 | 2022-08-01 | Adlai Nortye Biopharma Co Ltd | pd-1 antagonist |
CN115413275A (zh) * | 2020-02-03 | 2022-11-29 | 爱彼特生物制药公司 | 取代的1,1,-联苯化合物及其使用方法 |
PE20231067A1 (es) | 2020-02-14 | 2023-07-17 | Jounce Therapeutics Inc | Anticuerpos y proteinas de fusion que se unen a ccr8 y usos de estos |
CN113493469A (zh) * | 2020-03-18 | 2021-10-12 | 成都倍特药业股份有限公司 | 可作为免疫调节剂的化合物、其制备方法和应用 |
CN115605493A (zh) | 2020-03-20 | 2023-01-13 | 吉利德科学公司(Us) | 4′-c-取代的-2-卤代-2′-脱氧腺苷核苷的前药及其制备和使用方法 |
CN113444075B (zh) * | 2020-03-27 | 2024-06-21 | 中国医学科学院药物研究所 | 二氢吲哚衍生物、及其制法和药物组合物与用途 |
CN115835909A (zh) | 2020-05-05 | 2023-03-21 | 泰昂治疗公司 | 大麻素受体2型(cb2)调节剂和其用途 |
CN113637013A (zh) * | 2020-05-11 | 2021-11-12 | 上海长森药业有限公司 | 联芳环链接芳杂环衍生物作为免疫调节剂的制备及其应用 |
US20230278993A1 (en) * | 2020-05-22 | 2023-09-07 | Shanghai Longwood Biopharmaceuticals Co., Ltd. | Novel tricyclic aromatic heterocyclic compound and preparation method therefor, pharmaceutical composition and use thereof |
AU2021275118A1 (en) | 2020-05-22 | 2022-12-01 | Aligos Therapeutics, Inc. | Methods and compositions for targeting PD-L1 |
CN113880833A (zh) * | 2020-07-02 | 2022-01-04 | 上海翰森生物医药科技有限公司 | 联苯多环类衍生物抑制剂、其制备方法和应用 |
TW202214557A (zh) * | 2020-08-07 | 2022-04-16 | 大陸商上海再極醫藥科技有限公司 | 18f標記的聯苯類化合物、其中間體、製備方法、藥物組合物及應用 |
CN114075123B (zh) * | 2020-08-11 | 2023-06-06 | 中国人民解放军军事科学院军事医学研究院 | 苄胺类衍生物及其制备方法与用途 |
CA3190154A1 (en) * | 2020-08-17 | 2022-02-24 | Aligos Therapeutics, Inc. | Methods and compositions for targeting pd-l1 |
CA3194742A1 (en) | 2020-09-10 | 2022-03-17 | Nammi Therapeutics, Inc. | Formulated and/or co-formulated liposome compositions containing pd-1 antagonist prodrugs useful in the treatment of cancer and methods thereof |
CN118576599A (zh) * | 2020-10-23 | 2024-09-03 | 和记黄埔医药(上海)有限公司 | 一种药物组合产品在制备用于治疗非小细胞肺癌的药物中的用途 |
US11760756B2 (en) | 2020-11-06 | 2023-09-19 | Incyte Corporation | Crystalline form of a PD-1/PD-L1 inhibitor |
KR20230117573A (ko) | 2020-11-06 | 2023-08-08 | 인사이트 코포레이션 | Pd-1 및 pd-l1 억제제, 및 이의 염 및 결정형의 제조 방법 |
US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
CN112724148B (zh) * | 2020-12-29 | 2022-04-12 | 上海药明康德新药开发有限公司 | 一种咪唑并哒嗪类化合物及修饰后的双亲功能分子及其应用 |
CN116981660A (zh) * | 2021-03-22 | 2023-10-31 | 南京明德新药研发有限公司 | 氟代乙烯基联苯衍生物及其应用 |
CA3213088A1 (en) * | 2021-03-29 | 2022-10-06 | Vijay Ahuja | Substituted 1-aryl-1'-heteroaryl compounds, substituted 1,1'-biheteroaryl compounds, and methods using same |
TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | CD47/SIRPα結合及NEDD8活化酶E1調節次單元之共抑制以用於治療癌症 |
CN113121464B (zh) * | 2021-04-21 | 2023-02-24 | 药康众拓(江苏)医药科技有限公司 | 五元杂环取代的联苯类化合物及其制备方法和用途 |
CN113135895A (zh) * | 2021-04-30 | 2021-07-20 | 中国药科大学 | 一种新型联苯类衍生物及其制备方法与医药用途 |
EP4337223A1 (en) | 2021-05-13 | 2024-03-20 | Gilead Sciences, Inc. | Combination of a tlr8 modulating compound and anti-hbv sirna therapeutics |
CA3218475A1 (en) | 2021-05-21 | 2022-11-24 | Shipra DAS | Enhancing efficacy of t-cell-mediated immunotherapy by modulating cancer-associated fibroblasts in solid tumors |
CN113307779B (zh) * | 2021-05-25 | 2023-04-21 | 中国药科大学 | 杂环取代联苯类化合物、制备方法及用途 |
CN113304281B (zh) * | 2021-05-28 | 2024-07-09 | 新乡医学院 | PD-1siRNA联合氯喹在制备治疗直肠癌药物中的应用 |
WO2022271659A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
IL309378A (en) | 2021-06-23 | 2024-02-01 | Gilead Sciences Inc | DIACYLGLYERCOL KINASE MODULATING COMPOUNDS |
CA3222595A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
IT202100016775A1 (it) * | 2021-06-25 | 2022-12-25 | Univ Degli Studi Milano | Derivati triazinici per il trattamento dei tumori e di disturbi neurodegenerativi |
CN115677665B (zh) * | 2021-07-26 | 2024-04-19 | 中国药科大学 | 含联苯类衍生物及其医药用途 |
TW202325306A (zh) | 2021-09-02 | 2023-07-01 | 美商天恩治療有限公司 | 改良免疫細胞之生長及功能的方法 |
WO2023050104A1 (zh) * | 2021-09-28 | 2023-04-06 | 中国医学科学院药物研究所 | 二氢吲哚衍生物、及其制法和药物组合物与用途 |
EP4423078A1 (en) | 2021-10-28 | 2024-09-04 | Gilead Sciences, Inc. | Pyridizin-3(2h)-one derivatives |
MX2024005066A (es) | 2021-10-29 | 2024-05-24 | Gilead Sciences Inc | Compuestos de cd73. |
WO2023081730A1 (en) | 2021-11-03 | 2023-05-11 | Teon Therapeutics, Inc. | 4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide derivatives as cannabinoid cb2 receptor modulators for the treatment of cancer |
CN114539235A (zh) * | 2021-11-17 | 2022-05-27 | 药康众拓(江苏)医药科技有限公司 | 一种联苯类化合物、其制备方法和用途 |
WO2023097211A1 (en) | 2021-11-24 | 2023-06-01 | The University Of Southern California | Methods for enhancing immune checkpoint inhibitor therapy |
EP4444423A1 (en) | 2021-12-06 | 2024-10-16 | Helmholtz-Zentrum Dresden - Rossendorf e.V. | 3-((3-([1,1'-biphenyl]-3-ylmethoxy)phenoxy)methyl)benzonitrile derivatives and the use thereof |
WO2023107954A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
WO2023107956A1 (en) | 2021-12-08 | 2023-06-15 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
CN118488946A (zh) | 2021-12-22 | 2024-08-13 | 吉利德科学公司 | Ikaros锌指家族降解剂及其用途 |
CN118488948A (zh) | 2021-12-22 | 2024-08-13 | 吉利德科学公司 | Ikaros锌指家族降解剂及其用途 |
TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
AR128566A1 (es) * | 2022-02-18 | 2024-05-22 | Pattern Computer Inc | Combinaciones de fármacos y métodos para tratar el cáncer de ovario |
CN116768870A (zh) * | 2022-03-08 | 2023-09-19 | 中国科学院上海药物研究所 | 具有苄氧基芳基醚结构的化合物及其制备方法和用途 |
CN114591226B (zh) * | 2022-03-17 | 2024-09-17 | 南京益恩生物科技有限公司 | 一种烟醛衍生物的制备方法 |
EP4245756B1 (en) | 2022-03-17 | 2024-10-09 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
WO2023183817A1 (en) | 2022-03-24 | 2023-09-28 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
TW202345901A (zh) | 2022-04-05 | 2023-12-01 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
WO2023201267A1 (en) | 2022-04-13 | 2023-10-19 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
US20230374036A1 (en) | 2022-04-21 | 2023-11-23 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
US20240116928A1 (en) | 2022-07-01 | 2024-04-11 | Gilead Sciences, Inc. | Cd73 compounds |
WO2024015372A1 (en) | 2022-07-14 | 2024-01-18 | Teon Therapeutics, Inc. | Adenosine receptor antagonists and uses thereof |
WO2024019957A1 (en) * | 2022-07-18 | 2024-01-25 | Celgene Corporation | Compounds for the treatment of neurodegenerative diseases |
WO2024064668A1 (en) | 2022-09-21 | 2024-03-28 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPα DISRUPTION ANTICANCER COMBINATION THERAPY |
US20240165227A1 (en) | 2022-11-04 | 2024-05-23 | Gilead Sciences, Inc. | Anticancer therapies using anti-ccr8 antibody, chemo and immunotherapy combinations |
WO2024125662A1 (zh) * | 2022-12-16 | 2024-06-20 | 上海长森药业有限公司 | 新型联芳环化合物作为免疫调节剂的制备和应用 |
WO2024137852A1 (en) | 2022-12-22 | 2024-06-27 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
CN115844887B (zh) * | 2022-12-28 | 2023-09-08 | 中国人民解放军空军军医大学 | Selonsertib在制备治疗癌症的药物中的用途 |
EP4434987A1 (en) * | 2023-03-24 | 2024-09-25 | Affirma Biotech S. L. | Novel pd-l1 inhibitors |
WO2024215754A1 (en) | 2023-04-11 | 2024-10-17 | Gilead Sciences, Inc. | Kras modulating compounds |
WO2024220917A1 (en) | 2023-04-21 | 2024-10-24 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
CN116730940B (zh) * | 2023-06-13 | 2024-08-30 | 中国药科大学 | 杂环取代联苯类化合物及其医药用途 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150352206A1 (en) * | 2012-10-26 | 2015-12-10 | The University Of Chicago | Synergistic combination of immunologic inhibitors for the treatment of cancer |
US20160194307A1 (en) * | 2013-09-04 | 2016-07-07 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
Family Cites Families (152)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6319494B1 (en) | 1990-12-14 | 2001-11-20 | Cell Genesys, Inc. | Chimeric chains for receptor-associated signal transduction pathways |
IL104570A0 (en) | 1992-03-18 | 1993-05-13 | Yeda Res & Dev | Chimeric genes and cells transformed therewith |
US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
US7405295B2 (en) | 2003-06-04 | 2008-07-29 | Cgi Pharmaceuticals, Inc. | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
ES2873875T3 (es) | 2004-05-13 | 2021-11-04 | Icos Corp | Quinazolinonas como inhibidores de fosfatidilinositol 3-quinasa delta humano |
US20090142345A1 (en) | 2005-03-15 | 2009-06-04 | Takeda Pharmaceutical Company Limited | Prophylactic/therapeutic agent for cancer |
EP2439272A3 (en) | 2005-05-09 | 2013-07-31 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
AU2006265108C1 (en) | 2005-07-01 | 2013-01-17 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death ligand 1 (PD-L1) |
TWI382019B (zh) | 2005-08-19 | 2013-01-11 | Array Biopharma Inc | 作為類鐸受體(toll-like receptor)調節劑之胺基二氮雜呯 |
TWI404537B (zh) | 2005-08-19 | 2013-08-11 | Array Biopharma Inc | 作為類鐸受體(toll-like receptor)調節劑之8-經取代苯并氮雜呯 |
RU2498983C2 (ru) | 2007-03-12 | 2013-11-20 | Юм Биосайнсес Аустралия Пти Лтд | Соединения фениламинопиримидина и их применения |
PL2170888T3 (pl) | 2007-06-29 | 2015-09-30 | Gilead Sciences Inc | Pochodne puryn i ich zastosowanie jako modulatory receptora toll-podobnego 7 |
CN101842114A (zh) | 2007-08-02 | 2010-09-22 | 阿雷斯托生物科学股份有限公司 | 治疗和诊断纤维化、肿瘤侵入、血管生成和转移的方法和组合物 |
CA2743975C (en) | 2008-07-08 | 2018-09-11 | Incyte Corporation | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
JP5674155B2 (ja) | 2008-07-21 | 2015-02-25 | アポゲニクス ゲゼルシャフト ミット ベシュレンクテル ハフツングApogenix GmbH | Tnfsf一本鎖分子 |
ES2438496T3 (es) | 2008-08-01 | 2014-01-17 | Ventirx Pharmaceuticals, Inc. | Formulaciones de agonistas de receptores de tipo toll y su uso |
WO2010019702A2 (en) | 2008-08-12 | 2010-02-18 | Oncomed Pharmaceuticals, Inc. | Ddr1-binding agents and methods of use thereof |
US8450321B2 (en) | 2008-12-08 | 2013-05-28 | Gilead Connecticut, Inc. | 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor |
EA201692167A1 (ru) | 2008-12-09 | 2017-07-31 | Джилид Сайэнс, Инк. | Модуляторы толл-подобных рецепторов |
MX360800B (es) | 2009-05-13 | 2018-11-16 | Gilead Pharmasset Llc Star | Compuestos antivirales. |
TWI598347B (zh) | 2009-07-13 | 2017-09-11 | 基利科學股份有限公司 | 調節細胞凋亡信號之激酶的抑制劑 |
PT2467377T (pt) | 2009-08-18 | 2017-04-04 | Array Biopharma Inc | Benzoazepinas substituídas como moduladores de recetores de tipo toll |
BR112012003703A2 (pt) | 2009-08-18 | 2020-12-08 | Ventrix Phramaceuticals, INC. | Benzoazepinas substituídas como moduladores do receptor tipo toll |
US8962652B2 (en) | 2009-10-22 | 2015-02-24 | Gilead Sciences, Inc. | Derivatives of purine or deazapurine useful for the treatment of (inter alia) viral infections |
WO2011082400A2 (en) * | 2010-01-04 | 2011-07-07 | President And Fellows Of Harvard College | Modulators of immunoinhibitory receptor pd-1, and methods of use thereof |
CN105622757A (zh) | 2010-02-04 | 2016-06-01 | 吉联亚生物科技有限公司 | 结合赖氨酰氧化酶样2(loxl2)的抗体和其使用方法 |
US9186337B2 (en) | 2010-02-24 | 2015-11-17 | Oryzon Genomics S.A. | Lysine demethylase inhibitors for diseases and disorders associated with Hepadnaviridae |
WO2011146862A1 (en) | 2010-05-21 | 2011-11-24 | Bellicum Pharmaceuticals, Inc. | Methods for inducing selective apoptosis |
WO2011152351A1 (ja) | 2010-05-31 | 2011-12-08 | 小野薬品工業株式会社 | プリノン誘導体 |
ES2739505T3 (es) | 2010-08-27 | 2020-01-31 | Gilead Biologics Inc | Anticuerpos contra la metaloproteinasa 9 de la matriz |
RU2016118628A (ru) | 2010-10-01 | 2018-11-02 | Вентиркс Фармасьютикалз, Инк. | Способы лечения аллергических заболеваний |
EP2621500B1 (en) | 2010-10-01 | 2016-11-23 | Ventirx Pharmaceuticals, Inc. | Therapeutic use of a tlr agonist and combination therapy |
TR201820015T4 (tr) | 2010-12-09 | 2019-01-21 | Univ Pennsylvania | Kanser Tedavisi İçin Kimerik Antijen Reseptörü-Modifiye Edilmiş T Hücrelerinin Kullanılması |
UY33775A (es) | 2010-12-10 | 2012-07-31 | Gilead Sciences Inc | Inhibidores macrocíclicos de virus flaviviridae, composiciones farmacéuticas que los comprenden y sus usos |
EP3208263A1 (en) | 2011-01-12 | 2017-08-23 | VentiRx Pharmaceuticals, Inc. | Substituted benzoazepines as toll-like receptor modulators |
PL2663555T4 (pl) | 2011-01-12 | 2017-08-31 | Ventirx Pharmaceuticals, Inc. | Podstawione benzoazepiny jako modulatory receptora toll-podobnego |
SG192285A1 (en) | 2011-02-12 | 2013-09-30 | Globeimmune Inc | Yeast-based therapeutic for chronic hepatitis b infection |
EA027792B1 (ru) | 2011-04-08 | 2017-09-29 | Янссен Сайенсиз Айрлэнд Юси | Производные пиримидина для лечения вирусных инфекций |
KR102119700B1 (ko) | 2011-05-18 | 2020-06-08 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 바이러스 감염 및 기타 질환 치료용 퀴나졸린 유도체 |
TWI567061B (zh) | 2011-07-01 | 2017-01-21 | 吉李德科學股份有限公司 | 用於治療成癮之化合物 |
JP6101205B2 (ja) | 2011-08-23 | 2017-03-22 | 中外製薬株式会社 | 抗腫瘍活性を有する新規な抗ddr1抗体 |
GB201115529D0 (en) | 2011-09-08 | 2011-10-26 | Imp Innovations Ltd | Antibodies, uses and methods |
CA2850763A1 (en) | 2011-10-04 | 2013-04-11 | Gilead Calistoga Llc | Novel quinoxaline inhibitors of pi3k |
MY170062A (en) | 2011-11-29 | 2019-07-02 | Ono Pharmaceutical Co | Purinone derivative hydrochloride |
US8629274B2 (en) | 2011-12-21 | 2014-01-14 | Novira Therapeutics, Inc. | Hepatitis B antiviral agents |
UY34573A (es) | 2012-01-27 | 2013-06-28 | Gilead Sciences Inc | Inhibidor de la quinasa que regula la señal de la apoptosis |
WO2013116562A1 (en) | 2012-02-03 | 2013-08-08 | Gilead Calistoga Llc | Compositions and methods of treating a disease with (s)-4 amino-6-((1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile |
MY169159A (en) | 2012-02-08 | 2019-02-19 | Janssen R&D Ireland | Piperidino-pyrimidine derivatives for the treatment of viral infections |
US20130267517A1 (en) | 2012-03-31 | 2013-10-10 | Hoffmann-La Roche Inc. | Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
WO2013144129A1 (en) | 2012-03-31 | 2013-10-03 | F. Hoffmann-La Roche Ag | Novel 4-methyl-dihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
US8633182B2 (en) * | 2012-05-30 | 2014-01-21 | Boehringer Ingelheim International Gmbh | Indanyloxyphenylcyclopropanecarboxylic acids |
ES2656087T3 (es) | 2012-06-08 | 2018-02-23 | Gilead Sciences, Inc. | Inhibidores macrocíclicos de virus Flaviviridae |
CN104703991B (zh) | 2012-06-08 | 2018-03-23 | 吉利德科学公司 | 黄病毒科病毒的大环抑制剂 |
AR091279A1 (es) | 2012-06-08 | 2015-01-21 | Gilead Sciences Inc | Inhibidores macrociclicos de virus flaviviridae |
MX369417B (es) | 2012-08-10 | 2019-11-07 | Janssen Sciences Ireland Uc | Derivados de alquilpirimidina para el tratamiento de infecciones víricas y otras enfermedades. |
JP6285440B2 (ja) | 2012-08-28 | 2018-02-28 | ヤンセン・サイエンシズ・アイルランド・ユーシー | 融合二環式スルファモイル誘導体並びにb型肝炎の治療のための薬剤としてのその使用 |
JP2015533782A (ja) | 2012-08-28 | 2015-11-26 | ヤンセン・サイエンシズ・アイルランド・ユーシー | スルファモイル−アリールアミド及びb型肝炎の治療のための薬剤としてのその使用 |
MA37942B1 (fr) | 2012-09-10 | 2020-01-31 | Hoffmann La Roche | Hétéroaryldihydropyrimidines d'acide 6-aminé pour le traitement et la prophylaxie d'une infection par le virus de l'hépatite b |
AR092662A1 (es) | 2012-09-24 | 2015-04-29 | Gilead Sciences Inc | Anticuerpos anti-ddr1 |
CN107434803B (zh) | 2012-10-02 | 2020-05-05 | 吉利德科学公司 | 组蛋白去甲基化酶抑制剂 |
BR112015007586B1 (pt) | 2012-10-10 | 2021-02-09 | Janssen Sciences Ireland Uc | derivados de pirrolo[3,2-d]pirimidina, seu uso e composição farmacêutica que os compreende |
KR101268466B1 (ko) | 2012-11-12 | 2013-06-04 | 유병수 | 사축형 윈드 터빈 |
BR112015011036B1 (pt) | 2012-11-16 | 2022-02-01 | Janssen Sciences Ireland Uc | Derivados de 2-amino-quinazolina substituídos heterocíclicos, composição farmacêutica |
CN103848820A (zh) * | 2012-11-29 | 2014-06-11 | 广东东阳光药业有限公司 | 作为丙型肝炎抑制剂的螺环化合物及其在药物中的应用 |
US8987461B2 (en) | 2012-12-06 | 2015-03-24 | Quanticel Pharmaceuticals, Inc. | Histone demethylase inhibitors |
HUE037312T2 (hu) | 2012-12-19 | 2018-08-28 | Celgene Quanticel Res Inc | Hiszton demetiláz inhibitorok |
SG11201504946VA (en) | 2012-12-21 | 2015-07-30 | Quanticel Pharmaceuticals Inc | Histone demethylase inhibitors |
NZ708870A (en) | 2012-12-21 | 2016-09-30 | Gilead Calistoga Llc | Isoquinolinone or quinazolinone phosphatidylinositol 3-kinase inhibitors |
NZ708864A (en) | 2012-12-21 | 2016-09-30 | Gilead Calistoga Llc | Substituted pyrimidine aminoalkyl-quinazolones as phosphatidylinositol 3-kinase inhibitors |
KR102300861B1 (ko) | 2013-02-21 | 2021-09-10 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 바이러스 감염의 치료를 위한 2-아미노피리미딘 유도체 |
KR102229992B1 (ko) | 2013-02-27 | 2021-03-19 | 에피테라퓨틱스 에이피에스 | 히스톤 데메틸라아제의 저해제 |
EP2961732B1 (en) | 2013-02-28 | 2017-04-12 | Janssen Sciences Ireland UC | Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b |
WO2014165128A2 (en) | 2013-03-12 | 2014-10-09 | Novira Therapeutics, Inc. | Hepatitis b antiviral agents |
US9738637B2 (en) | 2013-03-12 | 2017-08-22 | Celgene Quantical Research, Inc. | Histone demethylase inhibitors |
WO2014139326A1 (en) | 2013-03-13 | 2014-09-18 | Genentech, Inc. | Pyrazolo compounds and uses thereof |
ES2731773T3 (es) | 2013-03-14 | 2019-11-19 | Celgene Quanticel Res Inc | Inhibidores de la histona desmetilasa |
SI2970211T1 (sl) | 2013-03-15 | 2017-12-29 | Quanticel Pharmaceuticals Inc. | Inhibitorji histon demetilaze |
MX353412B (es) | 2013-04-03 | 2018-01-10 | Janssen Sciences Ireland Uc | Derivados de n-fenil-carboxamida y su uso como medicamentos para el tratamiento de la hepatitis b. |
TWI527811B (zh) | 2013-05-09 | 2016-04-01 | 吉李德科學股份有限公司 | 作爲溴結構域抑制劑的苯並咪唑衍生物 |
AU2014267235B2 (en) | 2013-05-17 | 2017-10-05 | Janssen Sciences Ireland Uc | Sulphamoylthiophenamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
SG11201509463YA (en) | 2013-05-17 | 2015-12-30 | Hoffmann La Roche | 6-bridged heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
KR101709436B1 (ko) | 2013-06-14 | 2017-02-22 | 길리애드 사이언시즈, 인코포레이티드 | 포스파티딜이노시톨 3-키나제 억제제 |
CN104341407A (zh) | 2013-07-24 | 2015-02-11 | 黄传满 | 喹唑啉类化合物及其制备方法和用途 |
US10450270B2 (en) | 2013-07-25 | 2019-10-22 | Janssen Sciences Ireland Uc | Glyoxamide substituted pyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
US20160168155A1 (en) | 2013-07-30 | 2016-06-16 | Gilead Connecticut, Inc. | Polymorph of syk inhibitors |
EP3036237A4 (en) * | 2013-08-23 | 2017-01-25 | Fujian Haixi Pharmaceuticals Co. Ltd | Carboxylic acid compounds in treatment of diabetes mellitus |
KR101949251B1 (ko) | 2013-09-11 | 2019-02-18 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | B형간염바이러스 감염의 치료 방법 및 치료용 약학적 조성물 |
KR102290189B1 (ko) | 2013-10-23 | 2021-08-17 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 카르복스아미드 유도체 및 b형 간염 치료용 의약으로서의 이의 용도 |
CA2928003A1 (en) | 2013-11-14 | 2015-05-21 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis b infections |
UY35898A (es) | 2013-12-23 | 2015-07-31 | Gilead Sciences Inc | ?compuestos inhibidores de syk y composiciones que los comprenden?. |
US9290505B2 (en) | 2013-12-23 | 2016-03-22 | Gilead Sciences, Inc. | Substituted imidazo[1,2-a]pyrazines as Syk inhibitors |
US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
US9181288B2 (en) | 2014-01-16 | 2015-11-10 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
CN105899508B (zh) | 2014-01-30 | 2017-07-04 | 豪夫迈·罗氏有限公司 | 用于治疗和预防乙型肝炎病毒感染的新型二氢喹嗪酮类化合物 |
AU2015214961B2 (en) | 2014-02-06 | 2018-08-30 | Janssen Sciences Ireland Uc | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
UA117518C2 (uk) | 2014-03-07 | 2018-08-10 | Ф. Хоффманн-Ля Рош Аг | 6-конденсовані гетероарилдигідропіримідини для лікування та профілактики зараження вірусом гепатиту b |
US9400280B2 (en) | 2014-03-27 | 2016-07-26 | Novira Therapeutics, Inc. | Piperidine derivatives and methods of treating hepatitis B infections |
MX2016013159A (es) | 2014-04-10 | 2017-04-27 | Seattle Children's Hospital (Dba Seattle Children's Res Institute) | Expresion transgenica regulada por farmaco. |
RU2016146365A (ru) | 2014-05-13 | 2018-06-19 | Ф. Хоффманн-Ля Рош Аг | Новые дигидрохинолизиноны для лечения и профилактики заражения вирусом гепатита b |
EP3151820A4 (en) | 2014-06-06 | 2017-11-22 | Flexus Biosciences, Inc. | Immunoregulatory agents |
WO2016012470A1 (en) | 2014-07-25 | 2016-01-28 | F. Hoffmann-La Roche Ag | New amorphous and crystalline forms of (3s)-4-[[(4r)-4-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1, 4-dihydropyrimidin-6-yl]methyl]morpholine-3-carboxylic acid |
CA2952541C (en) | 2014-08-14 | 2019-10-01 | F. Hoffmann-La Roche Ag | Pyridazones and triazinones for the treatment and prophylaxis of hepatitis b virus infection |
JP2017526675A (ja) | 2014-08-27 | 2017-09-14 | ギリアード サイエンシーズ, インコーポレイテッド | ヒストンデメチラーゼを阻害するための化合物および方法 |
TWI751102B (zh) | 2014-08-28 | 2022-01-01 | 美商奇諾治療有限公司 | 對cd19具專一性之抗體及嵌合抗原受體 |
US10538555B2 (en) | 2014-09-11 | 2020-01-21 | Bristol-Myers Squibb Company | Macrocyclic inhibitors of the PD-1/PD-L1 and CD80(B7-1)/PD-L1 protein/protein interactions |
EP3194368B1 (en) | 2014-09-19 | 2020-12-23 | MacKay Medical Foundation the Presbyterian Church in Taiwan MacKay Memorial Hospital | Benzo-heterocyclic compounds and their applications |
ES2881195T3 (es) | 2014-09-26 | 2021-11-29 | Gilead Sciences Inc | Derivados de aminotriazina útiles como compuestos inhibidores de quinasas que se unen a TANK |
EP3204379B1 (en) | 2014-10-10 | 2019-03-06 | Genentech, Inc. | Pyrrolidine amide compounds as histone demethylase inhibitors |
US9637485B2 (en) | 2014-11-03 | 2017-05-02 | Hoffmann-La Roche Inc. | 6,7-dihydrobenzo[a]quinolizin-2-one derivatives for the treatment and prophylaxis of hepatitis B virus infection |
UY36390A (es) | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen |
US11266739B2 (en) | 2014-12-03 | 2022-03-08 | Juno Therapeutics, Inc. | Methods and compositions for adoptive cell therapy |
CA2966234A1 (en) | 2014-12-15 | 2016-06-23 | Bellicum Pharmaceuticals, Inc. | Methods for controlled elimination of therapeutic cells |
AR103222A1 (es) | 2014-12-23 | 2017-04-26 | Hoffmann La Roche | Procedimiento para la preparación de análogos de 4-fenil-5-alcoxicarbonil-2-tiazol-2-il-1,4-dihidropirimidina |
US9676793B2 (en) | 2014-12-23 | 2017-06-13 | Hoffmann-Laroche Inc. | Co-crystals of 5-amino-2-oxothiazolo[4,5-d]pyrimidin-3(2H)-yl-5-hydroxymethyl tetrahydrofuran-3-yl acetate and methods for preparing and using the same |
JP6506845B2 (ja) | 2014-12-30 | 2019-04-24 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | B型肝炎ウイルス感染症の治療及び予防のための新規テトラヒドロピリドピリミジン類及びテトラヒドロピリドピリジン類 |
WO2016107833A1 (en) | 2014-12-31 | 2016-07-07 | F. Hoffmann-La Roche Ag | A novel high-throughput method for quantification of hbv cccdna from cell lysate by real-time pcr |
MA41338B1 (fr) | 2015-01-16 | 2019-07-31 | Hoffmann La Roche | Composés de pyrazine pour le traitement de maladies infectieuses |
WO2016120186A1 (en) | 2015-01-27 | 2016-08-04 | F. Hoffmann-La Roche Ag | Recombinant hbv cccdna, the method to generate thereof and the use thereof |
JP6435054B2 (ja) | 2015-02-11 | 2018-12-05 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | B型肝炎ウイルス感染の治療及び予防のための新規2−オキソ−6,7−ジヒドロベンゾ[a]キノリジン−3−カルボン酸誘導体 |
EP3097102B1 (en) * | 2015-03-04 | 2017-10-18 | Gilead Sciences, Inc. | Toll-like receptor modulating 4,6-diamino-pyrido[3,2-d]pyrimidine compounds |
CU20170118A7 (es) | 2015-03-10 | 2018-02-08 | Aurigene Discovery Tech Ltd | Compuestos de tiadiazol y 1,2,4-oxadiazol 3-sustituidos como inmunomoduladores |
EA201791628A1 (ru) | 2015-03-10 | 2018-02-28 | Ауриджен Дискавери Текнолоджис Лимитед | Терапевтические циклические соединения в качестве иммуномодуляторов |
MX2017011614A (es) | 2015-03-10 | 2018-03-23 | Aurigene Discovery Tech Ltd | Compuestos de 1,3,4-oxadiazol y tiadiazol como inmunomoduladores. |
CN107427497A (zh) | 2015-03-10 | 2017-12-01 | 奥瑞基尼探索技术有限公司 | 作为免疫调节剂的3‑取代的1,3,4‑噁二唑和噻二唑化合物 |
JP6815686B2 (ja) | 2015-03-10 | 2021-01-20 | オーリジーン ディスカバリー テクノロジーズ リミテッドAurigene Discovery Technologies Limited | 免疫調節剤としての1,2,4−オキサジアゾールおよびチアジアゾール化合物 |
JP2018511647A (ja) * | 2015-04-12 | 2018-04-26 | ハンジョウ イノゲート ファーマ カンパニー リミテッドHangzhou Innogate Pharma Co.,Ltd. | Ido阻害剤とtdo阻害剤としての複素環化合物 |
CA2985642A1 (en) | 2015-05-15 | 2016-11-24 | Gilead Sciences, Inc. | Benzimidazole and imadazopyridine carboximidamide compounds having activity as inhibitors of indoleamine 2,3-dioxygenase |
WO2016196388A1 (en) | 2015-05-29 | 2016-12-08 | Juno Therapeutics, Inc. | Composition and methods for regulating inhibitory interactions in genetically engineered cells |
JP6816107B2 (ja) * | 2015-08-07 | 2021-01-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | インダニルアミノピリジルシクロプロパンカルボン酸、医薬組成物及びこれらの使用 |
MX2018003353A (es) | 2015-09-17 | 2018-09-17 | Novartis Ag | Terapias con celulas cart con una eficacia mejorada. |
US10745382B2 (en) | 2015-10-15 | 2020-08-18 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
EP3365340B1 (en) | 2015-10-19 | 2022-08-10 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
AU2016349501B2 (en) | 2015-11-04 | 2022-07-21 | Incyte Corporation | Pharmaceutical compositions and methods for indoleamine 2,3-dioxygenase inhibition and indications therefor |
HRP20221035T1 (hr) | 2015-11-19 | 2022-11-11 | Incyte Corporation | Heterociklički spojevi kao imunomodulatori |
EP3390361B1 (en) | 2015-12-17 | 2022-03-16 | Incyte Corporation | N-phenyl-pyridine-2-carboxamide derivatives and their use as pd-1/pd-l1 protein/protein interaction modulators |
AU2016379372A1 (en) | 2015-12-22 | 2018-08-02 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
EP3190103A1 (en) | 2016-01-08 | 2017-07-12 | Rijksuniversiteit Groningen | Inhibitors of the pd-1/pd-l1 protein/protein interaction |
US9798514B2 (en) | 2016-03-09 | 2017-10-24 | Spotify Ab | System and method for color beat display in a media content environment |
WO2017180769A1 (en) | 2016-04-13 | 2017-10-19 | Capten Therapeutics Inc. | Small molecules for immunogenic treatment of cancer |
WO2017192961A1 (en) | 2016-05-06 | 2017-11-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
WO2017202276A1 (zh) | 2016-05-23 | 2017-11-30 | 中国医学科学院药物研究所 | 苯醚类衍生物、及其制法和药物组合物与用途 |
BR112018073920A2 (pt) | 2016-05-26 | 2019-02-26 | Merck Patent Gmbh | inibidores de pd-1/pd-l1 para tratamento de câncer". |
EP3464279B1 (en) | 2016-05-26 | 2021-11-24 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
JP7000357B2 (ja) | 2016-06-20 | 2022-01-19 | インサイト・コーポレイション | 免疫調節剤としての複素環化合物 |
US10590105B2 (en) | 2016-07-08 | 2020-03-17 | Bristol-Meyers Squibb Company | 1,3-dihydroxy-phenyl derivatives useful as immunomodulators |
WO2018026971A1 (en) | 2016-08-03 | 2018-02-08 | Arising International, Llc | Symmetric or semi-symmetric compounds useful as immunomodulators |
US10563620B2 (en) | 2016-08-12 | 2020-02-18 | Rolls-Royce North American Technologies Inc. | Expandable exhaust cone |
MA46045A (fr) | 2016-08-29 | 2021-04-28 | Incyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
US10144706B2 (en) | 2016-09-01 | 2018-12-04 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
US10734026B2 (en) | 2016-09-01 | 2020-08-04 | Facebook, Inc. | Systems and methods for dynamically providing video content based on declarative instructions |
TW201823199A (zh) * | 2016-09-02 | 2018-07-01 | 美商北極星藥品公司 | 免疫檢查點抑制劑、組成物及其方法 |
-
2017
- 2017-04-20 JO JOP/2018/0040A patent/JOP20180040A1/ar unknown
-
2018
- 2018-04-18 BR BR102018007822-4A patent/BR102018007822A2/pt not_active Application Discontinuation
- 2018-04-19 WO PCT/US2018/028382 patent/WO2018195321A1/en active Application Filing
- 2018-04-19 PL PL18723183T patent/PL3612525T3/pl unknown
- 2018-04-19 KR KR1020247019039A patent/KR20240096808A/ko active Search and Examination
- 2018-04-19 TW TW107113386A patent/TWI783991B/zh active
- 2018-04-19 MX MX2019011431A patent/MX2019011431A/es unknown
- 2018-04-19 MA MA050147A patent/MA50147A/fr unknown
- 2018-04-19 AU AU2018256423A patent/AU2018256423B2/en active Active
- 2018-04-19 LT LTEPPCT/US2018/028382T patent/LT3612525T/lt unknown
- 2018-04-19 CA CA3175847A patent/CA3175847A1/en active Pending
- 2018-04-19 ES ES18723183T patent/ES2902360T3/es active Active
- 2018-04-19 PT PT187231832T patent/PT3612525T/pt unknown
- 2018-04-19 PE PE2019002066A patent/PE20200177A1/es unknown
- 2018-04-19 KR KR1020227006264A patent/KR102522886B1/ko active IP Right Grant
- 2018-04-19 DK DK18723183.2T patent/DK3612525T3/da active
- 2018-04-19 US US15/957,739 patent/US20180305315A1/en not_active Abandoned
- 2018-04-19 EP EP18723183.2A patent/EP3612525B1/en active Active
- 2018-04-19 CR CR20190478A patent/CR20190478A/es unknown
- 2018-04-19 HU HUE18723183A patent/HUE057506T2/hu unknown
- 2018-04-19 SG SG11201908619T patent/SG11201908619TA/en unknown
- 2018-04-19 EP EP21204444.0A patent/EP4026835A3/en active Pending
- 2018-04-19 TW TW112144378A patent/TW202432535A/zh unknown
- 2018-04-19 HR HRP20211920TT patent/HRP20211920T1/hr unknown
- 2018-04-19 CA CA3057864A patent/CA3057864C/en active Active
- 2018-04-19 CN CN201880040834.1A patent/CN110799509B/zh active Active
- 2018-04-19 TW TW111141601A patent/TWI835379B/zh active
- 2018-04-19 SI SI201830503T patent/SI3612525T1/sl unknown
- 2018-04-19 JP JP2019556921A patent/JP7161491B2/ja active Active
- 2018-04-19 CN CN202410937788.2A patent/CN118878461A/zh active Pending
- 2018-04-19 KR KR1020197033795A patent/KR102369506B1/ko active IP Right Grant
- 2018-04-19 KR KR1020237012587A patent/KR102674466B1/ko active IP Right Grant
- 2018-04-20 UY UY0001037690A patent/UY37690A/es not_active Application Discontinuation
-
2019
- 2019-09-19 IL IL26946619A patent/IL269466A/en unknown
- 2019-10-10 CL CL2019002895A patent/CL2019002895A1/es unknown
- 2019-10-17 CO CO2019011543A patent/CO2019011543A2/es unknown
- 2019-10-17 DO DO2019000266A patent/DOP2019000266A/es unknown
-
2020
- 2020-11-13 US US17/098,171 patent/US20210323922A1/en active Pending
-
2021
- 2021-02-01 AU AU2021200639A patent/AU2021200639B2/en active Active
-
2022
- 2022-01-05 CY CY20221100015T patent/CY1124891T1/el unknown
- 2022-05-31 JP JP2022088597A patent/JP7512323B2/ja active Active
- 2022-12-02 AU AU2022279537A patent/AU2022279537A1/en not_active Abandoned
-
2023
- 2023-10-02 JP JP2023171563A patent/JP2024009851A/ja active Pending
-
2024
- 2024-09-13 AU AU2024219711A patent/AU2024219711A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150352206A1 (en) * | 2012-10-26 | 2015-12-10 | The University Of Chicago | Synergistic combination of immunologic inhibitors for the treatment of cancer |
US20160194307A1 (en) * | 2013-09-04 | 2016-07-07 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI783991B (zh) | Pd‐1/pd‐l1抑制劑 | |
TWI796526B (zh) | Pd-1/pd-l1抑制劑 | |
JP7282112B2 (ja) | Hiv阻害剤化合物 | |
JP2022509526A (ja) | Hpk1阻害活性を有する置換6-アザベンゾイミダゾール化合物 | |
JP2024525160A (ja) | Pd-l1を標的とするための方法及び組成物 |